Bias in MRI Measurements of Apparent Diffusion Coefficient and Kurtosis: Implications for Choice of Maximum Diffusion Encoding

Tissue water diffusion is non-Gaussian and the expressions used to calculate diffusion parameters are approximations which introduce systematic errors dependent on the maximum diffusion encoding, diffusion time, etc. This study aimed at characterizing biases in estimates of both apparent diffusion coefficient and kurtosis, and determines their dependence on these parameters. Similar to the approach of several previous studies, Taylor expansion of the diffusion signal was used to calculate biases. Predicted errors were compared with data from one volunteer. Predicted errors agreed well with the measured errors and also the published diffusion tensor imaging measurements. The equations derived predict biases in measured diffusion parameters and explain much of the discrepancy between measurements obtained with different acquisition protocols. The equations may also be used to choose appropriate diffusion encoding for diffusion weighted, tensor, and kurtosis imaging

Acute-on-chronic Liver Failure: MELD Score 30-day Mortality Predictability and Etiology in a Pakistani Population

Background: Cirrhosis is a pathological condition that ultimately leads to liver failure. Acute on chronic liver failure (ACLF) has a high short term mortality rate. Viral hepatitis is the most common cause of liver failure in our local population. We carried out this study to identity the 30-day mortality and etiology of patients presenting with ACLF using Model for End-Stage Liver Disease (MELD) score predictability. Methodology: This was a descriptive case series, conducted at Sheikh Zayed Hospital, Lahore, Pakistan from January 31, 2018 to July 30, 2018. One hundred and eighty five patients who met the inclusion criteria were enrolled using 95% confidence level and 4% margin of error. Data was entered and analyzed with SPSS version 23.0. Numerical variables including age was presented by Mean ± S.D. Categorical variables i.e. gender, etiology of acute-on-chronic liver failure and 30-day mortality were presented by frequency and percentage. Data was stratified for age, gender, duration of chronic liver disease and MELD grade to address the effect modifiers. Post-stratification chi-square test was calculated using 95% significance (p≤0.05). Results: Majority of the enrolled patients were male (74.6%) while only 25.4% of the patients were female. One hundred and thirty patients (70.3%) had underlying viral hepatitis while twelve patients (6.5%) and forty three patients (23.2%) presented with alcoholic liver disease and drug-induced ACLF, respectively. Eighty patients (43.2%) died within 30 days of admission.The 30-day mortality with respect to MELD grade was statistically significant (p<0.001) with the highest mortality noted in grade-IV and thirty five patients (43.8%) dying within 30 days of admission (p<0.001). Grade-II and III MELD scores also contributed to the 30-day mortality with twenty three patients (28.8%) and nineteen patients (23.8%) dying within 30 days of admission (p<0.001). Conclusion: MELD scores are able to accurately predict the short-term mortality in patients with ACLF and viral hepatitis was the most common etiology in our population. Early detection and use of appropriate prognostic models may alleviate mortality and morbidity in paitents with ACLF

Effect of pioglitazone therapy on high sensitive C-reactive protein and lipid profile in diabetic patients with renal transplantation; a randomize clinical trial

Background: Inflammation has a major role in disease lead to renal failure and diabetes mellitus, controlling inflammation in diabetic kidney receivers could decrease morbidity and mortality. Objectives: This study designed for evaluating the efficacy of pioglitazone on C-reactive protein and lipid profile in diabetic kidney transplant receivers. Patients and Methods: In this double blinded clinical trial, 58 diabetic renal transplant receivers, in first month after transplantation, randomized into two groups; receiving insulin and pioglitazone (15 mg tablet daily, group A); and insulin and placebo (group B). Blood pressure, weight, body mass index (BMI) and laboratory data compared in before and after 4-month treatment in two groups by SPSS. Results: Fifty-eight patients with mean age of 44.15 ± 2 years included. There were no significant difference between groups in demographic data and other baseline measured variables (P > 0.05).The mean weigh and BMI were slightly increased in group A and decreased in group B. The mean hs-CRP was decreased 4.82 mg/dL in group A and 1.93 mg/dL in group B (P = 0.007). The mean total serum cholesterol was significantly decreased 34 mg/dL in group A and 18.07 mg/dL in group B (P = 0.027). The mean serum HDL-C was significantly increased 13.31 mg/dL in group A and 5.89 mg/dl in group B (P < 0.001). Conclusions: Pioglitazone seems to be a safe drug for reducing serum lipids and CRP in kidney transplant receivers with diabetes mellitus in short term. Long term effect of this drug could be evaluated in future studies. Copyright © 2015 The Author(s)

Bronchodilator, spasmolytic and calcium antagonist activities of Nigella sativa seeds (Kalonji): a traditional herbal product with multiple medicinal uses

Objective: The seeds of Nigella sativa locally known as Kalonji has been used in traditional medicine for the treatment of a variety of diseases including diarrhoea and asthma. The crude extract of N. sativa seeds (Ns.Cr) was studied in vitro for its possible spasmolytic and bronchodilator activities to rationalize the folkloric uses.Methods: Isolated rabbit jejunum and guinea-pig tracheal preparations were set up in Tyrode\u27s and Kreb\u27s solutions respectively and aerated with 5% CO2 in oxygen. Isotonic and isometric responses were measured on Bioscience oscillograph and Grass polygraph respectively.Results: The Ns.Cr caused a dose-dependent (0.1-3.0 mg/ml) relaxation of spontaneous contractions in rabbit jejunum. Ns.Cr also inhibited K(+)-induced contractions in a similar dose range, suggestive of calcium channel blockade (CCB). This effect was confirmed when pretreatment of the tissue with Ns.Cr, produced a dose-dependent shift in the Ca++ dose-response curves to the right similar to that of verapamil, a standard calcium channel blocker. In guinea-pig trachea, it caused relaxation of carbachol-, histamine- or K(+)-induced contractions indicating CCB. Activity-directed fractionation revealed that the CCB activity is concentrated in the petroleum ether fraction, which was found to be approximately 10 times more potent than the crude extract both in jejunum and tracheal preparations.Conclusion: These data indicate that the crude extract of Nigella sativa seeds exhibits spasmolytic and bronchodilator activities mediated possibly through calcium channel blockade and this activity is concentrated in the organic fraction. Its usefulness for diarrhoea and asthma in traditional medicine, appears thus to be based on a sound mechanistic background

Reply to Morone, G.; Giansanti, D. Comment on “Anwer et al. Rehabilitation of Upper Limb Motor Impairment in Stroke: A Narrative Review on the Prevalence, Risk Factors, and Economic Statistics of Stroke and State of the Art Therapies. Healthcare 2022, 10, 190”

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Peer reviewedFinal Published versio

Species and tissue-specificity of prokinetic, laxative and spasmodic effects of Fumaria parviflora

<p>Abstract</p> <p>Background</p> <p><it>Fumaria parviflora </it>Linn. (<it>Fumariaceae</it>), is a small branched annual herb found in many parts of the world including Saudi Arabia and Pakistan. This study was designed to provide pharmacological basis for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders.</p> <p>Methods</p> <p>The <it>in-vivo </it>prokinetic and laxative assays were conducted in mice. Isolated intestinal preparations (ileum and jejunum) from different animal species (mouse, guinea-pig and rabbit) were separately suspended in tissue baths containing Tyrode's solution bubbled with carbogen and maintained at 37°C. The spasmogenic responses were recorded using isotonic transducers coupled with PowerLab data acquisition system.</p> <p>Results</p> <p>The aqueous-methanol extract of <it>Fumaria parviflora </it>(Fp.Cr), which tested positive for the presence of alkaloids, saponins, tannins and anthraquinones showed partially atropine-sensitive prokinetic and laxative activities in the <it>in-vivo </it>in mice at 30 and 100 mg/kg. In the <it>in-vitro </it>studies, Fp.Cr (0.01-1 mg/ml) caused a concentration-dependent atropine-sensitive stimulatory effect both in mouse tissues (jejunum and ileum), and rabbit jejunum but had no effect in rabbit ileum. In guinea-pig tissues (ileum and jejunum), the crude extract showed a concentration-dependent stimulatory effect with higher efficacy in ileum and the effect was partially blocked by atropine, indicating the involvement of more than one types of gut-stimulant components (atropine-sensitive and insensitive). This could be a plausible reason for the greater efficacy of Fp.Cr in gut preparations of guinea-pig than in rabbit or mouse.</p> <p>Conclusions</p> <p>This study shows the prokinetic, laxative and spasmodic effects of the plant extract partially mediated through cholinergic pathways with species and tissue-selectivity, and provides a sound rationale for the medicinal use of <it>Fumaria parviflora </it>in gut motility disorders such as, indigestion and constipation. This study also suggests using different species to know better picture of pharmacological profile of the test material.</p

Form factors for B−−>πlνB-->\pi l\nu decay in a model constrained by chiral symmetry and quark model

The form factors for the $B-->\pi$ transition are evaluated in the entire momentum transfer range by using the constraints obtained in the framework combining the heavy quark expansion and chiral symmetry for light quarks and the quark model. In particular, we calculate the valence quark contributions and show that it together with the equal time commutator contribution simulate a B-meson pole q^2-dependence of form factors in addition to the usual vector meson B^{*}-pole diagram for $B --> \pi l\nu$ in the above framework. We discuss the predictions in our model, which provide an estimate of |V_{ub}|^2.Comment: 7 pages, Revtex, 5 figure, fig 3 is replaced and some text is adde

CD28 down-regulation on circulating CD4 T-cells is associated with poor prognoses of patients with idiopathic pulmonary fibrosis

Background: Although the etiology of idiopathic pulmonary fibrosis (IPF) remains perplexing, adaptive immune activation is evident among many afflicted patients. Repeated cycles of antigen-induced proliferation cause T-cells to lose surface expression of CD28, and we hypothesized this process might also occur in IPF. Methodology/Principal Findings: Peripheral blood CD4 T-cells from 89 IPF patients were analyzed by flow cytometry and cytokine multiplex assays, and correlated with clinical events. In comparison to autologous CD4 +CD28+cells, the unusual CD4+CD28 null lymphocytes seen in many IPF patients had discordant expressions of activation markers, more frequently produced cytotoxic mediators perforin (2.4±0.8% vs. 60.0±7.4%, p<0.0001) and granzyme B (4.5±2.8% vs.74.9±6.5%, p<0.0001), produced greater amounts of many pro-inflammatory cytokines, and less frequently expressed the regulatory T-cell marker FoxP3 (12.9±1.1% vs. 3.3±0.6% p<0.0001). Infiltration of CD4+CD28null T-cells in IPF lungs was confirmed by confocal microscopy. Interval changes of CD28 expression among subjects who had replicate studies were correlated with conterminous changes of their forced vital capacities (rs = 0.49, p = 0.012). Most importantly, one-year freedom from major adverse clinical events (either death or lung transplantation) was 56±6% among 78 IPF patients with CD4 +CD28+/CD4total≥82%, compared to 9±9% among those with more extensive CD28 down-regulation (CD4+CD28 +/CD4total<82%) (p = 0.0004). The odds ratio for major adverse events among those with the most extensive CD28 down-regulation was 13.0, with 95% confidence intervals 1.6-111.1. Conclusions/Significance: Marked down-regulation of CD28 on circulating CD4 T-cells, a result of repeated antigen-driven proliferations, is associated with poor outcomes in IPF patients. The CD4+CD28null cells of these patients have potentially enhanced pathogenic characteristics, including increased productions of cytotoxic mediators and pro-inflammatory cytokines. These findings show proliferative T-cell responses to antigen(s) resulting in CD28 down-regulation are associated with progression and manifestations of IPF, and suggest assays of circulating CD4 T-cells may identify patients at greatest risk for clinical deterioration. © 2010 Gilani et al